Del Potro, the 2009 US Open champion, has fallen from fourth to 484th in the rankings with a right wrist injury, but he beat Slovakian Lukas Lacko 6-1, 7-6 (7/1) to book a date with Hewitt, the 2001 US Open and 2002 Wimbledon champion.

Nishikori became the fourth seed to be sent packing, falling to 172nd-ranked US wild card Tim Smyczek 6-4, 3-6, 6-1.

Smyczek will face the winner of a later match between French second seed Gael Monfils, seeking his first title outside Europe, and American Robert Kendrick.